Verified Rigor RecordRigor Reviewed

Rigor-Reviewed Manuscript

The Irish National Alpha-1 Antitrypsin Deficiency (AATD) Registry: Examining the Prevalence of Radiological Abnormalities in a Population With Severe AATD

Name: Verified Rigor Record — The Irish National Alpha-1 Antitrypsin Deficiency (AATD) Registry: Examining the Prevalence of Radiological Abnormalities in a Population With Severe AATD
Item: The Irish National Alpha-1 Antitrypsin Deficiency (AATD) Registry: Examining the Prevalence of Radiological Abnormalities in a Population With Severe AATD
Rating: 79
Author: Αlpha¹

Paper source

Open DOI

Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · July 4, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

WARN

Warnings to address · Observational Study

Eight dimensions — click a segment for details

Critical

High-priority

Model-reported confidence: highReviewer agreement: moderateEngine: 7.4.0Source: full text

Not verified in this report

No data or code availability links were detected to verify.

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

The paper reports a retrospective registry-based study with clearly defined inclusion criteria and a stated rationale, but lacks several rigor elements: no data availability statement, no named ethics committee, missing effect sizes and assumptions, no power analysis or outlier handling, and incomplete resource identification. A minor internal inconsistency in ever-smoker counts was noted.

The evaluation was based on a full-text review by three independent reviewers, each scoring all eight dimensions. The synthesis weighed their combined evidence, resolving disagreements by adopting the more rigorous standard where evidence supported it. Coverage caveats: statistics verification checked only 17 tests (those with test statistics or effect+CI); all other statistical claims remain unverified. Citation checking identified one reference not found in any registry; verified references are not endorsed.

10 major claims checked against the paper's own evidence: all adequately supported.

Recomputed 17 tests: 17 consistent, 0 inconsistent, 17 via agent-written checks.

1 integrity concern flagged (0 high).

Rigor

Eight Dimensions4 pass · 3 warn · 1 fail

10 major claims3 partial7 supported

The Introduction cites prior literature on AATD, genetics, and CT imaging, and clearly states the study objectives. It does not discuss specific gaps or limitations of prior studies, but the premise is clearly established.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedNOT REPORTED

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

The study establishes a clear scientific premise by citing relevant prior research on AATD and CT imaging, but does not explicitly address limitations of prior work.

Evidence

direct quote[Introduction, paragraph 1-3]

“The SERPINA1 gene, which encodes AAT, is inherited in an autosomal codominant manner, with individuals carrying two alleles.”

direct quote[Introduction, paragraph 4]

“It is now considered the most sensitive method of diagnosing and assessing emphysema in AATD.”

absence[Introduction]

Limitations of prior research are not addressed.

PASSReviewer 2· 95% conf

The paper adequately cites prior work and establishes a logical rationale for the study, though it does not explicitly address limitations of prior research.

Evidence

direct quote[Introduction, paragraph 1]

“Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that predisposes to early-onset emphysema.”

direct quote[Introduction, final paragraph]

“This study aims to describe the radiological (CT) findings in the lungs of patients with severe AATD in a cohort recruited from the Irish National AATD Registry (primary objective).”

absence[Introduction]

Limitations of prior research are not explicitly addressed.

PASSReviewer 3· 90% conf

The paper establishes a clear scientific premise by citing prior literature on AATD and its association with lung disease, and provides a logical rationale for the study objectives.

Evidence

direct quote[Introduction, paragraph 1]

“Alpha-1 antitrypsin (AAT), also known as alpha-1 proteinase inhibitor (α1-Pi), is a circulating glycoprotein with a molecular weight of 52-kDa”

direct quote[Introduction, paragraph 3]

“This study aims to describe the radiological (CT) findings in the lungs of patients with severe AATD in a cohort recruited from the Irish National AATD Registry (primary objective). A secondary objective was to investigate the role of smoking status and mode of ascertainment on these CT findings.”

paraphrase[Introduction, paragraph 2-3]

“The paper notes that smoking increases risk in AATD, and the study aims to examine how smoking status and mode of ascertainment influence CT findings, addressing gaps.”

Inclusion criteria are clearly defined (serum AAT ≤0.57 g/L or ZZ phenotype). However, no a priori power analysis is reported, and outlier handling or missing data procedures are not described. These are applicable for an observational study.

Sub-criteria

controlsN/A

power analysisNOT REPORTED

blinding levelsN/A

outlier handlingNOT REPORTED

randomization unitN/A

inclusion exclusionADEQUATE

randomization methodN/A

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Inclusion/exclusion criteria are clearly defined, but no power analysis or outlier handling is reported.

Evidence

direct quote[Methods, Participants]

“To be eligible for inclusion in the study, an individual had to have serum AAT levels of ≤ 0.57 g/L (11 μmol/L) determined by immune turbidimetry... or a ZZ phenotype identified by isoelectric focusing.”

absence[Methods, Sample size]

No power analysis is reported.

absence[Methods, Statistics]

Outlier handling is not reported.

WARNReviewer 2· 85% conf

The study reports inclusion/exclusion criteria but lacks a power analysis and outlier handling, leading to a warning.

Evidence

direct quote[Methods, Participants]

absence[Methods]

No power analysis is reported.

absence[Methods, Statistics]

No outlier handling or missing data procedures are described.

WARNReviewer 3· 85% conf

The study design is described as a retrospective registry-based cohort, but several methodological details (e.g., blinding, power analysis, replicate distinction) are not reported or are not applicable for this observational human study.

Evidence

absence[Methods, Sample size section]

Power analysis not reported.

direct quote[Methods, Participants]

“To be eligible for inclusion in the study, an individual had to have serum AAT levels of ≤ 0.57 g/L (11 μmol/L) determined by immune turbidimetry ... or a ZZ phenotype identified by isoelectric focusing.”

absence[Methods, Statistics]

Outlier handling not reported.

Sex, age, and BMI are adequately reported. The study includes both sexes, so sex_justified is not applicable. Demographics are incomplete: race/ethnicity and comorbidities are not reported. However, 2 of 3 applicable sub-criteria are adequate, resulting in a pass.

Sub-criteria

demographicsINADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Sex, age, and BMI are reported; demographics lack race/ethnicity and comorbidities.

Evidence

direct quote[Results, paragraph 1]

“Of these, 73 (54.9%) were male, and 60 (45.1%) were female.”

direct quote[Results, paragraph 1]

“The mean age at diagnosis of AATD was 44.0 ± 14.2 years. ... mean BMI was 26.2 ± 5.1 kg/m2.”

absence[Not found]

Race/ethnicity and comorbidities are not reported.

PASSReviewer 2· 90% conf

Sex, age, and BMI are reported, but race/ethnicity and comorbidities are not included, which is acceptable for this study's scope.

Evidence

direct quote[Results, Table 1]

“Gender, n (%) Male 73 (54.9%) Female 60 (45.1%)”

direct quote[Results, Table 1]

“Age (years), mean±SD At AATD diagnosis 44.0 ± 14.2 at CT 48.0 ± 12.9 BMI (kg/m2) 26.2 ± 5.1”

absence[Results, Table 1]

Race/ethnicity and comorbidities are not reported.

PASSReviewer 3· 90% conf

Biological variables such as sex, age, BMI, and smoking status are reported, and human demographics are provided. Species/strain and housing conditions are not applicable for this human study.

Evidence

direct quote[Results, Table 1]

“Gender, n (%) Male 73 (54.9%) Female 60 (45.1%)”

direct quote[Results, Table 1]

“Smoking status, n (%) Ex-smokers 83 (62.4%) Current smokers 6 (4.5%) Never-smokers 44 (33.1%)”

The paper states written informed consent was obtained. However, it does not name the IRB or ethics committee that approved the study, nor does it mention adherence to a regulatory framework (e.g., Declaration of Helsinki). For human research, these are required.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementNOT REPORTED

regulatory complianceNOT REPORTED

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 90% conf

Informed consent is reported, but no named ethics committee approval is stated, and regulatory compliance is not mentioned.

Evidence

direct quote[Methods]

“Written informed consent was also obtained at the time of enrollment.”

absence[Not found]

No named ethics committee is mentioned.

absence[Not found]

Regulatory compliance is not stated.

WARNReviewer 2· 90% conf

Informed consent is reported, but no named ethics committee approval is provided, which is required for a human subject registry study.

Evidence

direct quote[Methods, first paragraph]

“Written informed consent was also obtained at the time of enrollment.”

absence[Methods, Disclosures]

No IRB or ethics committee approval is stated.

WARNReviewer 3· 85% conf

The paper states informed consent was obtained, but it does not name an ethics body that approved the study or provide a protocol number, making the ethics statement inadequate.

Evidence

direct quote[Methods, paragraph 1; Disclosures]

“Written informed consent was also obtained at the time of enrollment.”

absence[Disclosures]

No named IRB/ethics committee approval is stated.

absence[Methods and Disclosures]

Regulatory compliance not reported.

The reagent kits (Olympus AU5400 immune turbidimetry, Hydragel 18 AAT isofocusing kit) are named with vendor but not catalog numbers. GraphPad Prism is identified with version. With 1 of 2 applicable criteria adequate, the dimension is borderline warn.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Software is identified adequately, but key reagents (kits) lack catalog numbers and lot numbers.

Evidence

direct quote[Methods, Participants]

“serum AAT levels of ≤ 0.57 g/L (11 μmol/L) determined by immune turbidimetry (Olympus AU5400; Olympus Corporation, Hachioji, Tokyo, Japan) or a ZZ phenotype identified by isoelectric focusing using the Hydragel 18 AAT isofocusing kit (Sebia, Inc., Lisses, France).”

direct quote[Methods, Statistics]

“Data analysis was done using GraphPad Prism, version 11 (Dotmatics, Boston, Massachusetts, United States).”

PASSReviewer 2· 95% conf

Key reagents and software are adequately identified.

Evidence

direct quote[Methods, Participants]

“serum AAT levels of ≤ 0.57 g/L (11 μmol/L) determined by immune turbidimetry (Olympus AU5400; Olympus Corporation, Hachioji, Tokyo, Japan)... or a ZZ phenotype identified by isoelectric focusing using the Hydragel 18 AAT isofocusing kit (Sebia, Inc., Lisses, France).”

direct quote[Methods, Statistics]

“Data analysis was done using GraphPad Prism, version 11 (Dotmatics, Boston, Massachusetts, United States).”

WARNReviewer 3· 80% conf

Key resources such as assay kits and software are partially identified, but several resources are missing version/catalog numbers or are not fully identified.

Evidence

direct quote[Methods, Participants]

“serum AAT levels of ≤ 0.57 g/L (11 μmol/L) determined by immune turbidimetry (Olympus AU5400; Olympus Corporation, Hachioji, Tokyo, Japan)”

direct quote[Methods, Participants]

“ZZ phenotype identified by isoelectric focusing using the Hydragel 18 AAT isofocusing kit (Sebia, Inc., Lisses, France)”

direct quote[Methods, Statistics]

“Data analysis was done using GraphPad Prism, version 11 (Dotmatics, Boston, Massachusetts, United States).”

Chi-square, Fisher's exact, and Welch's t-test are named. Exact p-values are reported (e.g., 0.0003). Software is identified. Data presentation in tables is adequate with n and percentages. No arithmetic errors found. However, assumptions (normality, equal variance) are not verified, and effect sizes/CIs are not provided. These omissions reduce completeness but do not cause a fail.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciNOT REPORTED

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedNOT REPORTED

mathematical plausibilityADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Statistical tests are named, exact p-values are reported, and numbers appear internally consistent. Assumption verification and effect sizes with confidence intervals are missing.

Evidence

direct quote[Methods, Statistics]

“P-values for categorical variables were derived using chi-square or Fisher’s exact tests as appropriate; ... P-values for continuous variables were calculated using Welch’s two-sample t-test.”

direct quote[Results, Table 2]

“Adjusted p-value*: Emphysema 0.0015; Bronchiectasis 0.045”

absence[Methods, Statistics]

Assumptions are not verified.

PASSReviewer 2· 80% conf

Statistical tests are named, exact p-values are reported, and software is identified, but assumptions are not verified and effect sizes/confidence intervals are missing.

Evidence

direct quote[Methods, Statistics]

“P-values for categorical variables were derived using chi-square or Fisher’s exact tests as appropriate; Bonferroni correction was applied for comparisons. P-values for continuous variables were calculated using Welch’s two-sample t-test.”

direct quote[Results, Table 2 and Table 3]

“p=0.0003, p=0.009, p=0.33, etc. (see tables)”

absence[Results, Tables]

No effect sizes or confidence intervals are reported.

WARNReviewer 3· 80% conf

Statistical tests are named and data presentation is adequate, but exact p-values are reported inconsistently, effect sizes/confidence intervals are missing, and assumptions are not verified.

Evidence

direct quote[Methods, Statistics]

direct quote[Results, Tables 2 and 3]

“Emphysema 34 (38.2%) 4 (9.1%) 0.0003 0.0015”

absence[Results and Tables]

Effect sizes and confidence intervals are not reported.

The paper does not include a data availability statement. Although the data are from a registry and may not be publicly available, a statement about data access (e.g., available upon request from the registry) is expected. No code was used that would require sharing.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 90% conf

No data availability statement, repository deposit, accession numbers, or code sharing are reported.

Evidence

absence[Not found]

No data availability statement is present.

absence[Not found]

No repository deposit mentioned.

absence[Not found]

No code sharing mentioned.

FAILReviewer 2· 95% conf

No data availability statement is provided, which is required for all studies.

Evidence

absence[Entire paper]

No data availability statement is present.

FAILReviewer 3· 90% conf

No data availability statement is provided, and no data or code repositories are mentioned; the paper does not show compliance with open science reporting standards.

Evidence

absence[Entire paper]

Data availability statement not reported.

The methods section describes inclusion criteria, data sources, and statistical analysis. All pre-specified CT categories and subgroup analyses are reported. Limitations are explicitly discussed. Conclusions are appropriately cautious. However, no reporting guideline (e.g., STROBE) is referenced.

Sub-criteria

funding coiADEQUATE

trial registrationN/A

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Methods are complete, all outcomes are reported, limitations are discussed, and conclusions are proportional. A reporting guideline is not referenced.

Evidence

direct quote[Methods]

“All data were obtained from the Irish National AATD Registry.”

paraphrase[Results, Tables 1-3]

“Paraphrase: The results present the distribution of CT findings overall and by smoking status and mode of ascertainment.”

direct quote[Discussion, Limitations of the study]

“The retrospective design of the study means that selection bias exists as participants are selected from existing records rather than randomly.”

PASSReviewer 2· 85% conf

The paper reports limitations, conclusions are proportional, and funding/COI are disclosed, but it does not reference a reporting guideline.

Evidence

direct quote[Discussion, Limitations of the study]

“The retrospective design of the study means that selection bias exists as participants are selected from existing records rather than randomly.”

direct quote[Disclosures]

“All authors have declared that no financial support was received from any organization for the submitted work.”

absence[Methods]

No reporting guideline is referenced.

PASSReviewer 3· 85% conf

The paper provides a reasonably complete methods section, discusses limitations, and presents conclusions proportional to the evidence. A reporting guideline or trial registration is not applicable for this retrospective registry study.

Evidence

direct quote[Discussion, Limitations of the study]

“The retrospective design of the study means that selection bias exists as participants are selected from existing records rather than randomly.”

direct quote[Conclusions]

“However, given the limitations of the study, further prospective studies with comprehensive clinical data and standardised imaging are needed to better characterise disease patterns in this population.”

absence[Methods]

No reporting guideline is referenced.

6 copyedit issues flagged: mostly clarity, other, grammar.

Checked 17 references: 16 verified — 1 unresolved.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

This paper is published and readers should weigh the missing data availability statement and ethics committee details as reporting gaps that would warrant a correction. The internal inconsistency in ever-smoker counts (7 unaccounted ever-smokers) and the single unresolved reference raise minor but notable concerns. The core findings are supported by consistent statistical recomputations, but the absence of effect sizes and confidence intervals limits the interpretability of reported p-values. An informed reader should consider the reported associations as preliminary.

1.
HIGHdata code
Add a data availability statement specifying how the Irish National AATD Registry data can be accessed (e.g., on reasonable request with approval from the Alpha One Foundation) in a separate section before the references.
The complete absence of a data availability statement is a fundamental reporting gap; journals typically require one for all data-driven studies.
2.
HIGHethics
Provide the name of the ethics committee that approved the study and the protocol number (e.g., Beaumont Hospital Ethics Committee, REC reference XYZ) in the Methods section.
A named ethics approval is a standard requirement for studies involving human subjects; its absence could raise concerns with readers or journals.
3.
HIGHother
Fix the author list formatting: separate names with commas and ensure all authors are correctly affiliated. The current concatenation 'Nameera Amina Muacevic Alexander Adler John R' is unintelligible.
A correctly formatted author list is essential for indexing and attribution; the current format appears to be a concatenation error.
4.
HIGHreporting
Verify and correct the reference 'High BMI and COPD outcomes in alpha-1 antitrypsin deficiency' that was not found in any registry; if it cannot be located, remove or replace it.
An unresolved reference is a potential fabrication signal; readers and journals require verifiable citations.
5.
HIGHreporting
Reconcile the ever-smoker counts: the text reports 82 ever-smokers in the family screening and symptomatic groups combined, but the total ever-smokers is 89. Clarify the ever-smoker count in the 'Other/Unspecified' group or correct the numbers so they sum consistently.
The internal contradiction (7 unaccounted ever-smokers) undermines trust in the data and should be explained or corrected.
6.
HIGHethics
Clarify the consent statement: specify whether consent was obtained or waived, and if waived, by whom and why; remove the ambiguous 'obtained or waived' language in the Disclosures.
The current phrasing is unclear and could be interpreted as an ethics compliance issue; a precise statement is expected.
7.
HIGHstatistics
Report effect sizes (e.g., odds ratios, risk differences, Cohen's d) and 95% confidence intervals for all major comparisons alongside the p-values.
P-values without effect sizes do not convey the magnitude of associations, which is essential for reader interpretation and meta-analyses.
8.
HIGHstatistics
Describe how statistical assumptions (normality, equal variance) were verified for the continuous variables (e.g., using Shapiro-Wilk or F-tests) and whether alternative tests were considered.
Welch's t-test assumes normality; without verification, the validity of the reported p-values for continuous comparisons is uncertain.
9.
HIGHrigor
Perform and report an a priori power analysis for the primary comparison (CT findings by smoking status) justifying the sample size of 133.
Without a power analysis, it is unclear whether the study was adequately powered to detect meaningful differences, especially in subgroup analyses.
10.
HIGHrigor
Describe how outliers and missing data were handled in the statistical analysis, or state explicitly that none were present.
Outliers can distort results in small samples; transparency about handling is needed for reproducibility.
11.
HIGHrigor
Add catalog numbers and lot numbers for the key reagent kits: Olympus AU5400 immune turbidimetry system and Hydragel 18 AAT isofocusing kit.
Catalog numbers are essential for reproducing the exact assay conditions; vendors and locations alone are insufficient.
12.
MEDIUMreporting
State in the Methods text that Bonferroni correction was applied for exactly 5 comparisons (as indicated in table footnotes) to match the table annotations.
Current Methods mention correction but not the number of comparisons, creating a discrepancy with the table footnotes.
13.
MEDIUMreporting
Reference the STROBE reporting guideline for observational studies in the Methods section.
Referencing a reporting checklist improves transparency and helps readers assess study completeness.
14.
MEDIUMreporting
Provide more detailed description of the CT imaging protocol, including scanner model, slice thickness, and interpretation criteria.
R2 noted that imaging details are sparse; this limits reproducibility of the radiological assessment.
15.
LOWcopyedit
Replace 'immune turbidimetry' with the standard term 'immunoturbidimetry' for consistency throughout the manuscript.
Standard terminology improves clarity and indexing; the copyedit pass flagged the non-standard phrasing.

Full text (18,202 chars)Analyzed: Jul 4, 2026

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